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Functional impact of subunit composition and compensation on Drosophila melanogaster nicotinic receptors–targets of neonicotinoids

Neonicotinoid insecticides target insect nicotinic acetylcholine receptors (nAChRs) and their adverse effects on non-target insects are of serious concern. We recently found that cofactor TMX3 enables robust functional expression of insect nAChRs in Xenopus laevis oocytes and showed that neonicotino...

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Autores principales: Komori, Yuma, Takayama, Koichi, Okamoto, Naoki, Kamiya, Masaki, Koizumi, Wataru, Ihara, Makoto, Misawa, Daitaro, Kamiya, Kotaro, Yoshinari, Yuto, Seike, Kazuki, Kondo, Shu, Tanimoto, Hiromu, Niwa, Ryusuke, Sattelle, David B., Matsuda, Kazuhiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9934367/
https://www.ncbi.nlm.nih.gov/pubmed/36795653
http://dx.doi.org/10.1371/journal.pgen.1010522
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author Komori, Yuma
Takayama, Koichi
Okamoto, Naoki
Kamiya, Masaki
Koizumi, Wataru
Ihara, Makoto
Misawa, Daitaro
Kamiya, Kotaro
Yoshinari, Yuto
Seike, Kazuki
Kondo, Shu
Tanimoto, Hiromu
Niwa, Ryusuke
Sattelle, David B.
Matsuda, Kazuhiko
author_facet Komori, Yuma
Takayama, Koichi
Okamoto, Naoki
Kamiya, Masaki
Koizumi, Wataru
Ihara, Makoto
Misawa, Daitaro
Kamiya, Kotaro
Yoshinari, Yuto
Seike, Kazuki
Kondo, Shu
Tanimoto, Hiromu
Niwa, Ryusuke
Sattelle, David B.
Matsuda, Kazuhiko
author_sort Komori, Yuma
collection PubMed
description Neonicotinoid insecticides target insect nicotinic acetylcholine receptors (nAChRs) and their adverse effects on non-target insects are of serious concern. We recently found that cofactor TMX3 enables robust functional expression of insect nAChRs in Xenopus laevis oocytes and showed that neonicotinoids (imidacloprid, thiacloprid, and clothianidin) exhibited agonist actions on some nAChRs of the fruit fly (Drosophila melanogaster), honeybee (Apis mellifera) and bumblebee (Bombus terrestris) with more potent actions on the pollinator nAChRs. However, other subunits from the nAChR family remain to be explored. We show that the Dα3 subunit co-exists with Dα1, Dα2, Dβ1, and Dβ2 subunits in the same neurons of adult D. melanogaster, thereby expanding the possible nAChR subtypes in these cells alone from 4 to 12. The presence of Dα1 and Dα2 subunits reduced the affinity of imidacloprid, thiacloprid, and clothianidin for nAChRs expressed in Xenopus laevis oocytes, whereas the Dα3 subunit enhanced it. RNAi targeting Dα1, Dα2 or Dα3 in adults reduced expression of targeted subunits but commonly enhanced Dβ3 expression. Also, Dα1 RNAi enhanced Dα7 expression, Dα2 RNAi reduced Dα1, Dα6, and Dα7 expression and Dα3 RNAi reduced Dα1 expression while enhancing Dα2 expression, respectively. In most cases, RNAi treatment of either Dα1 or Dα2 reduced neonicotinoid toxicity in larvae, but Dα2 RNAi enhanced neonicotinoid sensitivity in adults reflecting the affinity-reducing effect of Dα2. Substituting each of Dα1, Dα2, and Dα3 subunits by Dα4 or Dβ3 subunit mostly increased neonicotinoid affinity and reduced efficacy. These results are important because they indicate that neonicotinoid actions involve the integrated activity of multiple nAChR subunit combinations and counsel caution in interpreting neonicotinoid actions simply in terms of toxicity.
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spelling pubmed-99343672023-02-17 Functional impact of subunit composition and compensation on Drosophila melanogaster nicotinic receptors–targets of neonicotinoids Komori, Yuma Takayama, Koichi Okamoto, Naoki Kamiya, Masaki Koizumi, Wataru Ihara, Makoto Misawa, Daitaro Kamiya, Kotaro Yoshinari, Yuto Seike, Kazuki Kondo, Shu Tanimoto, Hiromu Niwa, Ryusuke Sattelle, David B. Matsuda, Kazuhiko PLoS Genet Research Article Neonicotinoid insecticides target insect nicotinic acetylcholine receptors (nAChRs) and their adverse effects on non-target insects are of serious concern. We recently found that cofactor TMX3 enables robust functional expression of insect nAChRs in Xenopus laevis oocytes and showed that neonicotinoids (imidacloprid, thiacloprid, and clothianidin) exhibited agonist actions on some nAChRs of the fruit fly (Drosophila melanogaster), honeybee (Apis mellifera) and bumblebee (Bombus terrestris) with more potent actions on the pollinator nAChRs. However, other subunits from the nAChR family remain to be explored. We show that the Dα3 subunit co-exists with Dα1, Dα2, Dβ1, and Dβ2 subunits in the same neurons of adult D. melanogaster, thereby expanding the possible nAChR subtypes in these cells alone from 4 to 12. The presence of Dα1 and Dα2 subunits reduced the affinity of imidacloprid, thiacloprid, and clothianidin for nAChRs expressed in Xenopus laevis oocytes, whereas the Dα3 subunit enhanced it. RNAi targeting Dα1, Dα2 or Dα3 in adults reduced expression of targeted subunits but commonly enhanced Dβ3 expression. Also, Dα1 RNAi enhanced Dα7 expression, Dα2 RNAi reduced Dα1, Dα6, and Dα7 expression and Dα3 RNAi reduced Dα1 expression while enhancing Dα2 expression, respectively. In most cases, RNAi treatment of either Dα1 or Dα2 reduced neonicotinoid toxicity in larvae, but Dα2 RNAi enhanced neonicotinoid sensitivity in adults reflecting the affinity-reducing effect of Dα2. Substituting each of Dα1, Dα2, and Dα3 subunits by Dα4 or Dβ3 subunit mostly increased neonicotinoid affinity and reduced efficacy. These results are important because they indicate that neonicotinoid actions involve the integrated activity of multiple nAChR subunit combinations and counsel caution in interpreting neonicotinoid actions simply in terms of toxicity. Public Library of Science 2023-02-16 /pmc/articles/PMC9934367/ /pubmed/36795653 http://dx.doi.org/10.1371/journal.pgen.1010522 Text en © 2023 Komori et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Komori, Yuma
Takayama, Koichi
Okamoto, Naoki
Kamiya, Masaki
Koizumi, Wataru
Ihara, Makoto
Misawa, Daitaro
Kamiya, Kotaro
Yoshinari, Yuto
Seike, Kazuki
Kondo, Shu
Tanimoto, Hiromu
Niwa, Ryusuke
Sattelle, David B.
Matsuda, Kazuhiko
Functional impact of subunit composition and compensation on Drosophila melanogaster nicotinic receptors–targets of neonicotinoids
title Functional impact of subunit composition and compensation on Drosophila melanogaster nicotinic receptors–targets of neonicotinoids
title_full Functional impact of subunit composition and compensation on Drosophila melanogaster nicotinic receptors–targets of neonicotinoids
title_fullStr Functional impact of subunit composition and compensation on Drosophila melanogaster nicotinic receptors–targets of neonicotinoids
title_full_unstemmed Functional impact of subunit composition and compensation on Drosophila melanogaster nicotinic receptors–targets of neonicotinoids
title_short Functional impact of subunit composition and compensation on Drosophila melanogaster nicotinic receptors–targets of neonicotinoids
title_sort functional impact of subunit composition and compensation on drosophila melanogaster nicotinic receptors–targets of neonicotinoids
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9934367/
https://www.ncbi.nlm.nih.gov/pubmed/36795653
http://dx.doi.org/10.1371/journal.pgen.1010522
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